A protein complex expressed during terminal differentiation of monomyelocytic cells is an inhibitor of cell growth.
A protein complex (PC) composed of the MRP8 and MRP14 proteins has previously been shown to be a specific inhibitor of casein kinase I and II. This PC is expressed during the late stages of terminal differentiation induced in human promyelocytic HL-60 leukemia cells by 1 alpha,25-dihydroxyvitamin D3 and in human monocytic THP-1 leukemia cells by phorbol 12-myristate 13-acetate. This expression is associated with terminal cell differentiation because incubation of HL-60 cells with an agent or condition that causes suppression of growth but not induction of differentiation does not result in expression of the PC. At concentrations of 5-15 nM, the purified PC inhibited the growth of HL-60 cells and THP-1 cells, as well as other cell types belonging to different cell lineages. This growth inhibition was preceded by a reduction in [32P]phosphate incorporation and, at the higher PC concentrations, was associated with a reduction in [3H]thymidine, [3H]uridine, and [32S]methionine incorporation. The specific expression pattern and growth-inhibitory character of the PC suggests that the complex may have a role in suppressing cell growth during monomyelocytic terminal differentiation induced by specific chemical stimuli and during physiological and pathological events associated with monomyelocytic cell functions.
Murao
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S
Biological and Medical Research Division, Argonne National Laboratory, Illinois 60439.
Collart
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F
Huberman
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E
D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000502:physiology; D040501:Calgranulin A; D040502:Calgranulin B; D047388:Casein Kinases; D002454:Cell Differentiation / Q000502:physiology; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006131:Growth Inhibitors / Q000096:biosynthesis*; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism*; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000502:physiology; D010710:Phosphates / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D012265:Ribonucleotides / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000378:metabolism
D002135:Calcium-Binding Proteins; D040501:Calgranulin A; D040502:Calgranulin B; D004273:DNA, Neoplasm; D006131:Growth Inhibitors; D009363:Neoplasm Proteins; D010710:Phosphates; D047428:Protein Kinase Inhibitors; D012334:RNA, Neoplasm; D012265:Ribonucleotides; D008715:Methionine; D047388:Casein Kinases; D013936:Thymidine; D014529:Uridine